The new drug development process is a complex, time consuming and costly process. Not every compound that is tested in the laboratory is marketed but before it marketed; it has to undergo several stages of development called drug development. The drug development process converts potential drug candidates through
regulatory approval to the marketing. About 10,000 New Chemical Entities (NCE) investigated to potentially treat a disease, only 250 might make it to animal testing stage and of these; approximately 10 would qualify for testing in human. Between 19% and 30% of investigational new drug (INDs) that begins phase 1 trials make it to marketing.
Stages of Development of a New Drug
There are total three stages of Drug Development. They include;
A) Preclinical Stage
B) Clinical Stage
C) Regulatory Approval
Preclinical Stage of Drug Development Process
The preclinical stage comprises studies on animals to find out various parameters for a potential drug candidate under the process of development. During this stage, a sponsor (innovator) evaluates the drug’s toxic and pharmacological effects through in vitro testing and in vivo laboratory animal testing. At the preclinical stage, US FDA’s minimum requirement is that a sponsor should develop a pharmacological profile of the drug; determine its acute toxicity in at least two species of animals. Conduct short-term toxicity studies ranging from 2 weeks to 3 months, depending on the proposed duration of the candidate drug in the proposed clinical studies.
Clinical Stage of Drug Development Process
Clinical stage development of potential drug candidates comprises of pharmaceutical clinical trials, which are commonly conducted in 4 phases.
Phase 0:
- This is an exploratory phase of a clinical trial.
- Phase 0 trials are the first-in-human trials.
- Single sub therapeutic doses of the study drug are given to a small number of subjects (10 to 15) to gather preliminary data on the agent’s pharmacodynamics (what the drug does to the body) and pharmacokinetics (what the body does to the drugs).
- It is Also called as Micro Dosing Study.
Phase I:
- Here, the drug is tried in normal human volunteers (Elderly and children are left out).
- As the drug is not tested in the patients, so we cannot determine efficacy in this phase.
- Phase I studies are carried out in a small number of healthy volunteers, usually 20 to 100 volunteers.
- The study requires several months.
- Approximately 70% of drugs tested in this stage move to the next phase.
Phase II:
- This phase includes the early controlled clinical studies conducted to obtain some preliminary data on the effectiveness (Efficacy) of the potential drug for a particular indication.
- Testing in this phase help to determine the common short term side effects and risk associated with the drug under testing.
- The new drug at this stage is tested in small number of (20 – 300) patients.
- The length of study varies from several months to 2 years.
- Approximately 33% of drugs tested in this stage move to the next phase.
Phase III:
- In phase III trials, the treatment is given to large group of people to confirm its effectiveness, monitor side effects and compare it to commonly used treatments.
- If the drug is found to be harmless and effective in these trials, then one more application is filled with FDA (New Drug Application or NDA) to market the drug.
- Phase 3 studies usually includes 300 to 3000 people who have the disease or condition.
- The length of study varies from 1 to 4 years.
Phase IV:
- This phase is also known as Post Marketing Surveillance (PMS) and is carried out once the candidate drug is approved as a drug and marketed as a medicinal product.
- This phase aims to find out the drug safety profile in a large patient pool across the world and to establish its safety profile.
- The post-launch safety monitoring helps to detect rare or long-term adverse effects of the drug over a large patient’s population.
- In this phase Ethical Clearance Is Not Essential.
Regulatory Approval Stage of Drug Development Process
Investigational New Drug Application
- Once the candidate drug is tested in animals (preclinical testing), a sponsor files IND with regulatory authority for getting approval for testing it in humans.
- The IND application includes information such as; results of previous experiments; how, where, and by whom the new studies will be conducted; the chemical structure of the candidate drug; how it works in the body (mechanism of action); any toxic effect found in the animal studies; and how it is manufactured.
- The IND must be reviewed and approved by the Institutional Review Board (IRB).
New Drug Application
- New Drug Application (NDA) is filled just after the phase 3 stage.
- The NDA application is the medium through which new drug sponsors formally propose that the regulatory authority approve this drug for sale and marketing in the country of approval.
- The goals of the NDA are to provide enough information to permit regulatory reviewers to give approval for marketing.